We propose to investigate several aspects of avian osteopetrosis, a neoplasm characterized by excessive and disorganized bone deposition. A plaque-purified strain of avian leukosis virus will be injected into group-specific antigen and chicken-helper-factor free embryos, and chicks which develop osteopetrosis will be investigated. We propose to develop an in vitro transformation assay for avian osteopetrosis, using cultured embryonic bone and bone cells. Target cells will be characterized by culturing various organs of the chick embryo, and infecting with the plaque-purified osteopetrosis virus. We will determine whether a cooperativity is required between the cells of different organs for transformation, or whether the product of one cell (such as a hormone) is required for the transformation of another. The effect of parathyroid hormone and calcitonin on in vitro transformation will be assessed. We propose to determine whether osteopetrosis in the mouse is caused by a virus. We will attempt to find an osteopetrosis virus in the grey-lethal strain of mice, which possess an autosomal recessive gene for osteopetrosis. Techniques for the induction of latent viruses will be used to determine if a virus is present, and if so, the oncogenic potential of the virus will be established. The successful isolation of an osteopetrosis virus of mice would lead to searches for similar viruses of other mammals, and would implicate a similar causitive agent in man.